Department of Epidemiology and Cancer Control, St. Jude's Children's Research Hospital, Memphis, TN, USA.
Department of Diagnostic Imaging, St. Jude's Children's Research Hospital, Memphis, TN, USA.
JNCI Cancer Spectr. 2022 Mar 2;6(2). doi: 10.1093/jncics/pkac026.
Long-term survivors of pediatric acute lymphoblastic leukemia are at elevated risk for neurocognitive deficits and corresponding brain dysfunction. This study examined sex-based differences in functional neuroimaging outcomes in acute lymphoblastic leukemia survivors treated with chemotherapy alone.
Functional magnetic resonance imaging (fMRI) and neurocognitive testing were obtained in 123 survivors (46% male; median [min-max] age = 14.2 years [8.3-26.5 years]; time since diagnosis = 7.7 years [5.1-12.5 years]) treated on the St. Jude Total XV treatment protocol. Participants performed the n-back working memory task in a 3 T scanner. Functional neuroimaging data were processed (realigned, slice time corrected, normalized, smoothed) and analyzed using statistical parametric mapping with contrasts for 1-back and 2-back conditions, which reflect varying degrees of working memory and task load. Group-level fMRI contrasts were stratified by sex and adjusted for age and methotrexate exposure. Statistical tests were 2-sided (P < .05 statistical significance threshold).
Relative to males, female survivors exhibited less activation (ie, reduced blood oxygen dependent-level signals) in the right parietal operculum, supramarginal gyrus and inferior occipital gyrus, and bilateral superior frontal medial gyrus during increased working memory load (family-wise error-corrected P = .004 to .008, adjusting for age and methotrexate dose). Female survivors were slower to correctly respond to the 2-back condition than males (P < .05), though there were no differences in overall accuracy. Performance accuracy was negatively correlated with fMRI activity in female survivors (Pearson's r = -0.39 to -0.29, P = .001 to .02), but not in males.
These results suggest the working memory network is more impaired in female survivors than male survivors, which may contribute to ongoing functional deficits.
儿科急性淋巴细胞白血病的长期幸存者存在神经认知缺陷和相应脑功能障碍的风险增加。本研究检测了单纯化疗治疗的急性淋巴细胞白血病幸存者的功能神经影像学结果中的性别差异。
在接受圣裘德全 XV 治疗方案治疗的 123 名幸存者（46%为男性；中位数[最小-最大]年龄=14.2 岁[8.3-26.5 岁]；诊断后时间=7.7 年[5.1-12.5 年]）中获得了功能磁共振成像（fMRI）和神经认知测试。参与者在 3T 扫描仪中执行 n-back 工作记忆任务。使用统计参数映射对功能神经影像学数据进行处理（重对齐、切片时间校正、归一化、平滑）和分析，使用 1 回和 2 回条件的对比进行分析，这反映了不同程度的工作记忆和任务负荷。基于性别对组水平 fMRI 对比进行分层，并根据年龄和甲氨蝶呤暴露进行调整。统计检验为双侧（P<.05 为统计学显著阈值）。
与男性相比，女性幸存者在增加工作记忆负荷时，右侧顶叶脑回、缘上回和枕下回以及双侧额上回内侧回的激活程度较低（经校正的全脑错误率校正 P=0.004 至 0.008，调整年龄和甲氨蝶呤剂量）。女性幸存者对 2 回条件的正确反应速度比男性慢（P<.05），尽管整体准确性没有差异。表现准确性与女性幸存者的 fMRI 活动呈负相关（Pearson's r=-0.39 至-0.29，P=0.001 至 0.02），但在男性中没有相关性。
这些结果表明，女性幸存者的工作记忆网络受损程度比男性幸存者更严重，这可能导致持续的功能缺陷。
